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    Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection


    Swann, Rachael E. and Cowton, Vanessa M. and Robinson, Mark W. and Cole, Sarah J. and Barclay, Stephen T. and Mills, Peter R. and Thomson, Emma C. and McLauchlan, John and Patel, Arvind H. (2016) Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection. Journal of Virology, 36 (12). ISSN 0022-538X

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    Abstract

    During hepatitis C virus (HCV) infection,broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glyco proteins are generated in many individuals.It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses inindividuals with chronic infection we reassociated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with srong cross-genotypic E1E2 binding (P=0.03). Overall,we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergeno type neutralization did not correlate with any clinical parameters;however,analysis of individuals with genotype1(gt1) HCVinfection(n=20),using an intrageno type pseudop article panel,found a stronga ssociation between neutralization breadth and reduced liver fibrosis(P=0.006).Abroad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA DQB1 gene (P=0.038),as previously reported in a cohort with acute disease. Furthermore,the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses inpatients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses.

    Item Type: Article
    Keywords: Broad Anti-Hepatitis C Virus; HCV; Antibody Responses; Improved Clinical Disease Parameters; Chronic HCV Infection;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12658
    Identification Number: https://doi.org/10.1089/jir.2015.0169
    Depositing User: Mark Robinson
    Date Deposited: 30 Mar 2020 10:13
    Journal or Publication Title: Journal of Virology
    Publisher: American Society for Microbiology
    Refereed: Yes
    URI:

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